Abeona Therapeutics announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding its Biologics License Application (BLA) for prademagene zamikeracel (pz-cel) for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). The CRL follows the completion of the FDA's Late Cycle Review Meeting in March 2024.
The FDA indicated that certain additional Chemistry, Manufacturing, and Controls (CMC) information must be satisfactorily resolved before the application can be approved. These requirements pertain to validation for manufacturing and release testing methods, some of which were noted during the FDA’s pre-license inspection (PLI). Abeona submitted plans to provide CMC data before BLA approval, with full validation reports to follow, but the FDA stated the proposed timeline wouldn't allow sufficient review by the May 25, 2024, PDUFA date.
No Clinical Deficiencies Identified
Importantly, the CRL did not cite any deficiencies related to the clinical efficacy or safety data included in the BLA. The FDA has not requested any new clinical trials or additional clinical data to support the approval of pz-cel.
Vish Seshadri, Chief Executive Officer of Abeona, expressed disappointment but affirmed the company's commitment to providing the necessary CMC information. "We are already hard at work generating the additional CMC information, and we expect that all of FDA’s requests will be addressable in a reasonable timeframe," Seshadri stated. Abeona anticipates completing the BLA resubmission in the third quarter of 2024 with updates to address all deficiencies outlined in the CRL.
Background on Pz-cel and RDEB
Pz-cel is an investigational autologous, COL7A1 gene-corrected epidermal sheet being developed for RDEB, a rare connective tissue disorder caused by a defect in the COL7A1 gene. This defect prevents the production of Type VII collagen, which is essential for skin integrity. Pz-cel is designed to introduce a functional collagen-producing COL7A1 gene into a patient’s own skin cells, enabling long-term gene expression through stable integration into the dividing target cell genome using a retroviral vector.
The BLA for pz-cel is supported by data from the pivotal Phase 3 VIITAL™ study (NCT04227106) and a Phase 1/2a study (NCT01263379). These studies suggest that a single application of pz-cel on large, chronic wounds can lead to sustained wound healing and pain reduction. The Phase 3 VIITAL™ study was a randomized clinical trial that evaluated the efficacy, safety, and tolerability of pz-cel in 43 large chronic wound pairs in 11 subjects with RDEB.
Pz-cel has been granted Regenerative Medicine Advanced Therapy, Breakthrough Therapy, Orphan Drug, and Rare Pediatric Disease designations by the FDA. Abeona manufactures pz-cel at its gene and cell therapy manufacturing facility in Cleveland, Ohio.
